Schizotypal personality disorder (SPD) is of intrinsic interest as a personality disorder. It is also theoretically and experimentally important as a likely component of the schizophrenia spectrum disorders: recent genetic-epidemiologic studies have provided strong evidence of a link between SPD and schizophrenia (SZ), thereby emphasizing the utility of the strategy of studying SPD in order to examine the SZ spectrum abnormalities without the complicating, and often confounding variables present in SZ, such as chronic illness, chronic medication, and chronic hospitalization. SPD subjects thus may, we believe, provide a more non-confounded and clearer view of at least some of the "primary" spectrum abnormalities and/or markers of vulnerability than SZ subjects. Accordingly, this application proposes to extend our multidisciplinary research program for probing the biological bases of SZ to the study of SPD. We think this focus on SPD is particularly timely because many of SPD's biologic correlates remain unexamined. We have developed clinical, neuropsychological. event-related potential (ERP) and magnetic resonance imaging (NM) methodologies which, together with our conceptual and theoretical approach, have, we believe, proven to be very fruitful in SZ studies. We believe this approach to SPD will prove equally fruitful, since our own and others' data strongly suggest that at least some of the functional, clinical and brain abnormalities of SZ may also be present in this spectrum disorder. Our new preliminary and multidisciplinary SPD data provide what we believe is striking and exciting evidence for congruence with the abnormalities present in SZ, and which we think are likely to be primarily referable to temporal lobe, to prefrontal. cortex and to their joint systems. SPD subjects show: 1) a relatively specific deficit in verbal learning (primarily semantic clustering) on the California Verbal Learning Test (CVLT) and a trend toward Wisconsin Card Sorting Task (WCST) abnormalities; 2) P300 event-related potential overall amplitude reduction and a left < right temporal region voltage asymmetry (the P300 measures processing of unusual stimuli); and 3) NM evidence for left-lateralized reduction in volume of the anterior hippocampus/amygdala and enlargement of adjacent temporal horn. This application proposes to confirm and to extend these findings in a 5-year study of 25 male and 25 female right-handed individuals with DSM-III-R SPD diagnoses and 50 age-, sex-, and parent al SES-matched normal controls. The feasibility of this application's ambitious technical and theoretical goals, is, we believe, validated by our extensive experience with the methodology and approach in SZ research.